Immunotherapeutic targeting of CD133 in adult brain tumors and understanding tumor microenvironment in Glioblastoma

Glioblastoma (GBM) is an aggressive adult brain tumor, and in spite of standard of care (SOC) with radiation therapy and chemotherapy with temozolomide tumor re-growth (or recurrence) and patient relapse are inevitable. There is compelling evidence that suggests SOC can debulk the tumor but cells endowed with treatment-resistant properties (e.g. expressing the protein marker CD133) could escape such therapies and initiate tumor relapse. Brain metastases (BM) are the most common and fatal brain tumors, and current SOC does not extend survival past 12 months. We identified BM cells to also express high levels of CD133, whose expression correlates with disease progression, recurrence, chemo- and radio-resistance and overall poor prognosis. We propose to test immune cells called NK /T cells with a synthetic protein that binds to CD133, allowing these NK/T cells to recognize CD133 on tumor cells and destroy them. In-house in vitro and in vivo GBM and BM patient-derived models will be used to test novel constructs supplied from our industry partner Century Therapeutics (CD133- CARNK/T). On the other hand, we will explore GBM tumor immune microenvironment (TIME) by performing integrative multiomics of primary and recurrent patient-matched GBMs including RNA seq, sciRNA seq and proteomics.

Faculty Supervisor:

Sheila Kumari Singh;Thomas Kislinger;Jason Moffat

Student:

Partner:

Century Therapeutics

Discipline:

Life Sciences

Sector:

Professional, scientific and technical services

University:

McMaster University; University of Toronto

Program: